Physical and social environments shape the behavior of all animals from prenatal life through adulthood, producing effects that include physiological, cellular and molecular changes in the brain. The long-term objective of this research is to understand how social interactions produce changes in the brain at the level of behavior, circuitry, neurons and genes. Since social rank is a ubiquitous element in social systems and rank position can dramatically influence the quality of an individual's life, we will analyze how changes in status alter brain structure and function. We will continue using a well-defined teleost fish model system in which we manipulate the social status of animals under controlled laboratory conditions mimicking natural events and measure the cellular and molecular consequences in identified neurons. We have previously shown that the social environment alone can cause these neurons to enlarge or shrink ca. 8-fold in volume and that their dendritic extent and interconnections depend critically on social status. We will use novel, complementary approaches to discover how behavior causes these changes in the brain. 1) We will collect the contents of the single identified neurons that show a large response to social signals as they ascend in social status. We will sequence the gene transcripts produced in these neurons during social ascent and identify the gene transcripts to identify the sequelae of gene expression patterns responsible for changes in neuronal size and connectivity. We will analyze the transcripts using cutting edge bioinformatic tools to identify the architecture of molecular expression that causes changes in the brain. This novel information will reveal the molecular underpinnings of cellular and physiological changes and its ontogeny during status change. 2) We will identify functional changes and connections among the status sensitive neurons to identify how they change in response to social signals of rank. The neurons we study must integrate social and physiological inputs allowing us to identify pathways that control them by exploiting animals in their two extreme phenotypes, high status and low status as well as animals during transitions between these states. Social ascent has behavioral and molecular signatures distinct from social descent that we will use to understand the differences in the underlying mechanisms of control. We know that the neurons under study differ in their function between high status animals where they fire synchronously while in low status animals where they fire asynchronously. We will identify the mechanisms that account for these different functions at the cellular and network levels. Dominance hierarchies are a central organizing mechanism for animal societies and status is known to regulate access to resources and impact survival, health, and reproduction. Yet little is known about how social rank acts biologically to alter the brain and behavior. The results from the experiments proposed here should provide insights into mechanisms through which social signals that indicate status can change cells and circuits in vertebrate brains. Since social status regulates social behavior similarly in most species, our results will provide useful information for understanding how such potent social signals influence the brain that will ultimately be important for improving public health.

Public Health Relevance

Social rank is a ubiquitous element in social systems and rank position can dramatically influence the quality of an individual's life. This research is directed at understanding how changing social rank and more generally, how social behavior changes the brain. Rank must alter health through specific biological mechanisms and this project is directed at understanding how social stratification alters brain structures.